26th ESICM ANNUAL CONGRESS — PARIS, FRANCE — 5–9 OCTOBER 2013
for 30 min. Diagnosis of VAP was based upon CPIS score and clinical criteria (1). For
cytokines determination was used ELISA.
RESULTS. 41 patients were included, 11 (26 %) developed VAP. APACHE II 24 ± 7.
Development of VAP was associated with higher ICU stay, time under MV and mortality.
Baseline Those who developed VAP presented worst pO2/FiO2 ratio 152 vs 259 (p \ 0.01).
In 24 % of patients was identified a microorganism, (26 % of non-VAP patients and 18 % in
VAP-patients, in which were multi-resistant). VAP-patients, showed significantly higher
TNF-a blood levels 7.6 vs 5.5 pg/ml (p \ 0.05); MBAL TNF-a and IL-6 levels were lower
6.4 vs 19.6 pg/ml (p 0.08) and 5.4 vs 9.2 pg/ml (p 0.06) respectively. There were nodifferences with other cytokines or biomarkers.CPR or hs-CPR were not detectable in EBC.
Follow-Up: VAP-patients: in three cases (27 %), causal microorganism was present inprevious cultures. With regard to cytokines and biomarkers: blood TNF and MBAL IL-8
levels were significantly lower in samples previous to diagnosis of VAP (6.6 vs 7.7 pg/ml
and 446 vs 2,460 pg/ml respectively). Those who developed VAP, at diagnosis, presented
significant higher levels of: blood IL-8 and CRP; and MBAL, hs-CRP. PCT was also higher
in blood and MBAL but not significantly.
CONCLUSIONS. Only in 27 % of patients who developed VAP, precious cultures were
helpful in diagnosis. We could not find a definite profile of any cytokine or biomarker that
could anticipate diagnosis of VAP. Blood levels of IL-8 and CRP and MBAL levels of hsCRP and PCT are elevated in VAP patients.
REFERENCE(S).
1. ATS, IDSA. Guidelines for the management of VAP. Am J Respir Crit Care Med. 2005.
2. Bayley DL. Validation of assays for inflammatory mediators in exhaled breath condensate. Eur Respir J. 2008.
GRANT ACKNOWLEDGMENT. This study was sponsored by Pfizer.

0781
HIGH DOSE NEBULIZED AMIKACIN: A PILOT STUDY IN VENTILATEDPATIENTS WITH HEALTHCARE ASSOCIATED PNEUMONIAOBJECTIVES. The aim of the study is to describe the pharmacokinetics (PK) of CMS of
two different critically ill populations of patients, obese vs. regular weight using a loadingdose of 4.5 MU of CMS.
METHODS. A clinical trial (MagicBullet) is in progress at the ICUs of Virgen del Rocı́oUniversity Hospital, Seville, Spain, since January of 2012. Critically ill patients who met thefollowing inclusion criteria were enrolled: Age C 18 years, [96 h of mechanical ventilation,
ventilator-associated pneumonia, CPIS [ 4, tracheo-bronchial culture, non-pregnant women,
and normal renal function. The following data was collected: gender, age, weight, height,
APACHE II score, body max index (BMI), plasma creatinine (Cr) and creatinine clearance(CLCR) on days 1 (1st CMS dose) and 3 (7th CMS dose), using the Cockcroft–Gault formula.
Patients were treated with a loading dose of CMS of 4.5 MU (360 mg, 1 h infusion,
followed by 3 MU (240 mg) every 8 h (30 min infusion). Venous blood samples weredrawn after the loading dose at 1, 2, 4, and 8 h after the beginning of the CMS infusion andat the steady state (7th dose) at 1, 4, and 8 h after the beginning of the CMS infusion. All
blood samples were immediately chilled and centrifuged, and the plasma was stored at 70 C until assayed. Plasma colistin concentrations were determined by a HPLC–MS/MS
method. A non-compartmental analysis of data was done (PKSolver 2.0). Due to the small
number of cases in each group, only descriptive analyses were performed (SPSS 15.0).
RESULTS. Seven patients have been included: four in the obese group and three in theregular weight group. Demographic, clinical, and PK data are shown in Tables 1, 2 and 3.
No deterioration of renal function was observed during the study in any of the patients
included. With regard to the PK at the steady state important differences in the maximum
plasma colistin concentrations (total colistin and unbound colistin) 1.89 vs. 3.42 and 0.62 vs.
1.13 were found between obese and regular weight patients.
CONCLUSIONS. Although a higher number of patients have to be included to confirm theseresults, it looks like the actual dose regimen used for the treatment of obese patients is suboptimal.
If these results are confirmed with the inclusion of more patients a higher dose of colistin forobese patients should be considered to treat severe infections caused by MDR bacteria.
GRANT ACKNOWLEDGMENT. MagicBullet is a project funded by the European
Union–Directorate General for Research and Innovation through the Seventh Framework
Program for Research and Development (Grant Agreement 278232) and has been runningsince January 1st 2012 (duration 36 months).
Table 1 Demographic and clinical data
No APACHE II Demographic data
Score
Gender Age (year) Weight (kg) Height BMI Diagnosis

S. Ehrmann1, F. Darrouzain2,3, T. Boulain4, D. Garot1, E. Masseret1, A. Petitcollin2,3,
A. Legras1, E. Mercier1, J. Badin1, A. Guillon1,5, D. Ternant2,3, L. Vecellio5, D. Perrotin1,
G. Paintaud2,3, P.-F. Dequin1
1

CHRU de Tours, Service de réanimation polyvalente, Tours, France, 2Université François
Rabelais, Faculté de Médecine, UMR CNRS 7292, Equipe GICC, Tours, France, 3CHRU deTours, Laboratoire de pharmacologie-toxicologie, Tours, France, 4Hôpital de la Source,
Centre Hospitalier Régional d’Orléans, Réanimation médicale polyvalente, Orléans, France,
5
Université François Rabelais, Faculté de Médecine, Centre d’Etude des Pathologies
Respiratoires, INSERM U1100/EA6305, Tours, France
INTRODUCTION. High-dose nebulized antibiotics, as a complement to intravenous treatment, may improve pneumonia treatment efficacy, thanks to increased concentrations at the siteof infection. Up to 60 mg/Kg of amikacin have been successfully nebulized in animal studies
and to healthy subjects undergoing mechanical ventilation1,2. However, the pharmacokinetics
and safety of such high doses have not been assessed in patients suffering of pneumonia.
OBJECTIVES. To evaluate serum pharmacokinetics and safety of 60 mg/Kg amikacin
nebulization during mechanical ventilation
METHODS. Patients undergoing invasive mechanical ventilation with a suspicion of
hospital acquired, healthcare- or ventilator-associated pneumonia were included. Aside of
an intravenous betalactam antibiotic, each patient received 20 mg/Kg amikacin intravenously at inclusion; thereafter amikacin was administered qd. for 3 days: 60 mg/Kg
nebulized (prototype jet-nebulizer in a dry circuit or with a heated humidifier) or 20 mg/Kg
intravenously. 10 serum concentration of amikacin were measured over 24 h after eachadministration for non-compartmental pharmacokinetic analysis. Safety/efficacy data wererecorded until day 10. Patients in whom pneumonia was not confirmed (amikacin sensitivebacterial documentation) or experiencing a side effect linked to amikacin administration
were excluded from the study, but safety assessment was pursued until day 10.
RESULTS. 22 patients were included in the study, after informed consent. Six patients were
excluded because pneumonia was not confirmed (n = 5) or because of renal failure before thesecond amikacin administration (n = 1), leaving 16 patients with at least 2 amikacin administrations: median age 59 years (interquartile range 51–72); n = 2 female; weight 75 Kg (63–78);
body mass index 26 Kg/m2 (24–28); baseline serum creatinine 62 lmol (51–73).
Overall 32 nebulizations were analysed: 4.5 g (4.1–4.9) nebulized over 2h15 (1h31–2h48);
the area under the serum amikacin concentration curve (AUC) was 27 mg h/L (13–46),
significantly lower than the AUC after intravenous administration: 396 mg h/L (paired
p \ 0.01). Serum bioavailability was 2.8 % (2.1–4.8), not significantly different, wether ornot, active humidification was present. Without humidification, two patients experienced
tracheal tube obstruction possibly related to amikacin nebulization, whereas this never
happened in case of active humidification.
CONCLUSIONS. Nebulization of up to 60 mg/Kg appeared feasible in intubated patients.
Systemic toxicity is very unlikely to occur as serum AUC appeared well below those observed
after intravenous infusion. Active humidification may prevent tracheal tube obstruction without
significant changes in bioavailability and thus in probable alveolar drug deposition.
REFERENCES. 1. Goldstein I et al. Am J Respir Crit Care Med. 2002; 166: 1357–81.
2. Ehrmann S et al. Int Care Med. 2008; 34: 755–62.

1

2

3

4

M.E. Pachón-Ibáñez , F. Doboco , A. Gutiérrez-Valencia , A. Puppo-Moreno ,A. Gutiérrez-Pizarraya5, R. Ruiz-Valderas3, E. Fernández-Hinojosa4, C. Milara-Ibáñez5,
S.R. Leal-Noval4, P. Moreno-Martı́nez3, R. Amaya4, C. Rosso6, L. López-Cortes7,
J.M. Cisneros5, J. Garnacho-Montero4
1
Hospital Universitario Virgen del Rocı́o/Instituto de Biomedicina de Sevilla (IBiS),
Infectious Diseases, Sevilla, Spain, 2University Hospital Macarena, Microbiology, Sevilla,
Spain, 3University Hospital Virgen del Rocı́o/Instituto de Biomedicina de Sevilla (IBiS),
Infectious Diseases, Sevilla, Spain, 4University Hospital Virgen del Rocı́o, Critical Care andEmergency, Sevilla, Spain, 5University Hospital Virgen del Rocı́o, Infectious Diseases,
Sevilla, Spain, 6University Hospital Virgen del Rocı́o, Pharmacology Clinical, Sevilla,
Spain, 7University Hospital Virgen del Rocı́o, Sevilla, Spain
INTRODUCTION. Although it is known the difficulty of the antimicrobial dosing in obese
patients so far there are no pharmacokinetic studies of colistin for these kinds of patients.

1

25

M

68

120

174

39.6

2

19

M

47

80

178

25.3

VAP

3

17

M

76

110

175

35.9

VAP

4

26

F

67

90

150

40

VAP

5

24

F

57

57

168

20.2

VAP

6

12

M

54

100

185

29.2

VAP

7

15

M

68

150

164

55.7

VAP

Table 2 Renal function data
Plasma creatinine (mg/dL)

VAP

Creatinine clearance (mL/min)

No Creatinine level Creatinine level Creatinine
Creatinine
Day 1
Day 3
clearance Day 1
clearance Day 3
1

0.67

0.54

179.10222.22

2

0.75

0.75

137.78137.78

3

1.36

1.29

71.90

75.80

4

0.51

0.39

152.08198.88

5

0.9

1.16

62.06

48.15

6

0.79

0.99

151.20120.65

7

0.47

0.35

319.15428.57

Table 3 Pharmacokinetics data
Loading dose
(1st dose)

Steady state(7th dose)

Obese Regular Obese Regularweightweight0782
PHARMACOKINETICS OF COLISTIN AFTER THE ADMINISTRATION
OF A LOADING DOSE OF 4.5 MU OF COLISTIN METHANESULFONATE (CMS)IN OBESE CRITICALLY ILL PATIENTS VERSUS REGULAR WEIGHTCRITICALLY ILL PATIENTS

S433

Total colistin

Cmax (lg/mL)

2.71

2.62

1.89

Total colistin

Tmax (h)

2.00

2.00

2.00

3.42
4.00

Total colistin

T1/2 (h)

12.37

9.11

14.89

21.38

Total colistin

AUC0–8 h (lg/mL 9 h)

14.57

15.37

10.99

22.75

Unbound colistin fCmax (lg/mL)

0.94

0.87

0.62

1.13

Unbound colistin fTmax (h)

2.00

2.00

2.00

4.00

Unbound colistin fT1/2 (h)

10.67

8.72

14.59

20.79

Unbound colistin fAUC0-8 h (lg/mL 9 h)

4.87

5.06

3.56

7.51

0783

EVALUATING THE AMBU ASCOPETM 3 SYSTEM FOR BRONCH-ALVEOLARLAVAGE AND BRONCHIAL WASH IN INVASIVELY VENTILATED PATIENTS
B.A. McGrath1, A.M. Bentley1
1

University Hospital of South Manchester, Acute Intensive Care Unit, Manchester, UK
INTRODUCTION. The Ambu aScopeTM 3 system is a novel disposable bronchoscope(5.5 mm maximum external diameter with 2.2 mm suction/working channel) which connects to a separate portable aViewTM monitor. The range of tip movement is 150 upwards
and 130 downwards. We report the first observations in practice of this system for bronchalveolar lavage (BAL) and bronchial wash (BW) in invasively ventilated patients.
OBJECTIVES. To evaluate the functionality and ease of use of the aScopeTM 3 system.
METHODS. 20 CE-marked aScopeTM three bronchoscopes and two aViewTM monitors
were supplied by Ambu for the evaluation. Patients receiving invasive mechanical ventilation via endotracheal or tracheostomy tube who had a clinical indication for either BAL

S434

26th ESICM ANNUAL CONGRESS — PARIS, FRANCE — 5–9 OCTOBER 2013or BW were included. Ten procedures were carried out by each author, both of whom areexperienced bronchoscopists. A 5-point Likert scale was used (1 fully disagree, 3 neutral, 5fully agree) to evaluate functionality and ease of use of the system, applied to ten statements
concerning functionality (see Table 1). Number of major lung segments visualised (out of 6)along with overall impressions of performance (satisfactory: yes/no) and whether theoperator felt that the aScopeTM three system could replace our existing non-disposable
system (yes/no) were also recorded.
RESULTS. All 20 procedures (7 BW only, 4 BAL only, 9 both BW and BAL) werecompleted between 26/2/13 and 9/4/13 by the 2 authors (10 procedures each). Data were
explored using the Shapiro–Wilk test and the results (mean Likert scores for functionality
and ease of use) shown in Table 1. All six major segments of the bronchial tree werevisualised for all endoscopies. Overall functionality and performance was rated as satisfactory in all procedures and the system was felt to be able to replace the existing nondisposable system in 19 procedures.
Table 1 Mean Likert scores for functionality
Mean

95 % CI

Easy to advance bronchoscope

4.9

4.6–5.1

Easy to inject via working channel

4.6

4.3–4.8

Ease of performing suction

4.4

4.1–4.8

Suction capability adequate

4.4

4.1–4.7

Functionality of working channel satisfactory

3.7

2.9–4.5

Image quality adequate to perform procedure

4.7

4.4–4.9

Lens clearing was easy

4.3

4.0–4.6

Lightweight handle was a benefit

3.2

2.0–3.4

Easy to record images on aViewTM monitor

2.7

1.7–3.6

CONCLUSIONS. Our evaluation by two independent, experienced clinicians has demonstrated that the Ambu aScopeTM three system was assessed as easy to use and performs
satisfactorily for BAL and BW in invasively ventilated critically ill patients. The system isportable and easy to assemble and position at the bedside and although the monitor display issmaller and of lower resolution (800 9 480 pixel, 8.5 in. colour TFT LCD screen) than our
non-disposable ‘stack’ system, image quality was good enough to perform the procedures.
The suction capabilities were comparable to our non-disposable bronchoscope. The lowest
scores were in relation to the functionality of the aViewTM monitor, which had pre-releasesoftware installed. The lightweight handle was not perceived as a particular advantage in thisevaluation, although this did not affect the overall impressions of functionality. The disposable nature of the system may have infection control and cost advantages.
GRANT ACKNOWLEDGMENT. Ambu provided a donation to our ICU research fundfor conducting this evaluation.

0784
INSPIRATORY FLOW BIAS AND THE INCIDENCE OF VAP
J.A.D.S.B. Salge1, C.M. Neiva1, M.S. Volpe2
University of Franca, Franca, Brazil, 2Federal University of Triangulo Mineiro, Uberaba,
BrazilINTRODUCTION. Ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in the intensive care unit (ICU). VAP prolongs the duration of mechanicalventilation (MV) and hospital stay, and increases mortality. Since the 1980s, there has been
increasing evidence that ventilator settings can produce a flow bias that may clear or embedmucus during MV. The ratio between the peak inspiratory flow (PIF) and the peak expiratory flow (PEF), or the difference between the two, are described as possible criticalfactors that may influence secretion movement.
OBJECTIVES. To investigate in mechanically ventilated patients the effect of flow bias on
the incidence of VAP.
METHODS. Participated in the study patients under MV for \24 h and that were expected
to continue under MV for [72 h. Exclusion criteria were: suspicion of pneumonia prior toMV, aspiration during intubation and severe hypoxemia. Respiratory mechanics were registered at the time of entering in the study and every each 12 h during the first 60 h using
CO2SMO monitor. VAP diagnostic was made based on new or worsening radiographic
infiltrates and leukocytosis or leucopenia, fever or purulent sputum. Total time of MV, ICU
and hospital lengths were registered. Patients that developed VAP were classified as VAPgroup and patients that did not presented VAP as control group. Statistical analysis was
performed using unpaired t-test or Mann–Whitney and a two-way analysis for repeatedmeasures as appropriate.
RESULTS. 30 patients were included in the study, 17 of them presented VAP (Table 1).
Although the differences were not significant, the VAP group compared to the control group
was older and had a slightly higher APACHE score. Total time of MV, ICU and hospital
lengths were significantly higher in the VAP group compared to the control.

1

Table 1

There were no differences between the PIF/PEF ratio (p = 0.080) and the PEF - PIF
difference (p = 0.110) during the first 60 h of MV between the two groups. The mean ± SE
PIF/PEF ratio and PEF - PIF difference were in the VAP group 1, 5 ± 0.5 and - 14.1 ±1.5 and in the control 1.6 ± 0.7 and - 17.5 ± 1.4, respectively.
CONCLUSIONS. These preliminary results of a current study suggest that an inspiratory
flow bias during the first 60 h of MV does not influence the incidence of VAP. Both groups,
VAP and control, were ventilated with a PIF/PFE ratio much higher than the thresholddescribed in the literature—PIF/PFE ratio [ 0.9—which, theoretically, is sufficient to move
mucus towards the lungs. The negative mean PEF–PIF differences, in both groups, also
indicated that secretion was moved deeper into the lungs. As expected, patients with VAP
had longer time of MV, ICU and hospital length.

0786
EFFECT OF DIFFERENT TRACHEAL TUBE CUFF MATERIAL, SHAPE AND
SIZE FOR FLUID LEAKAGE ACROSS THE CUFF

Fig. 1 A view monitor

Fig. 2 A scope 3 and a view monitor

N. Harayama1, K. Nagata1, Y. Isa1, M. Nakamura2, T. Endo1, A. Kanazawa1, H. Arai1,
S. Nihei1, K. Aibara1, M. Kamochi1, T. Sata2
1
University of Occupational and Environmental Health, University Hospital, Critical Care
Medicine, Kitakyushu-City, Japan, 2University of Occupational and Environmental Health,
Department of Anesthesiology, Kitakyushu-City, JapanINTRODUCTION. Micro aspiration of oral secretions across the tracheal tube cuff is oneof the most important causes of ventilator-associated pneumonia (VAP). The formation offolds in the inflated cuff is the major cause of micro aspiration and the cuff material andshape affect the leakage volume across the cuff. Although there are various types of tracheal
tubes, the effects of each tube size to cuff leakage are not clear. Even if the internal diameteris same size, cuff size and shape are different greatly in each tube type.
OBJECTIVES. To compare fluid leakage across the cuff in each different tracheal tube
type and size in a bench-top model.
METHODS. We compared fluid leakage across the cuff in a bench-top model. Tracheal
tubes were inserted into a vertical artificial glass trachea with 22 mm internal diameter. Fourdifferent types of tracheal tubes with secretion drainage, SealGuard Evac with polyurethane
cuff (Covidien), TaperGuard Evac (Covidien) with polyvinylchloride cuff, Hi-Lo Evac with
polyvinylchloride cuff (Covidien), Portex BlueLine SACETT with polyvinylchloride cuff
(Smiths Medical), and five different sizes (6.5, 7.0, 7.5, 8.0, 8.5 mm internal diameter) of
each tube type were used in this study. Intracuff pressure was set at 25 cmH2O. 20 ml dyedwater was applied above the unlubricated tube cuff and fluid leakage was measured at
2 min. Each experiment was carried out five times. Data were shown as mean ± SEM (ml).
RESULTS. Figure 1 showed the relation between the tube size and fluid leakage across thecuff in different tube types. Tube size to minimize the cuff leakage was different by eachtube type. Taper shape cuff with both polyvinylchloride and polyurethane showed similar
property.
CONCLUSIONS. Each tracheal tube has its own property in the view of cuff fluid leakage.
These results indicate that the best tracheal tube size to prevent VAP is different in each tube
type. We need to pay attention not only to tube internal diameter but also to cuff size in eachtracheal tube to avoid trachea–cuff size mismatch.